PREPARATION AND IN VITRO CHARACTERIZATION OF LIDOCAINE LOADED ALOE VERA GEL FORMULATION FOR THE TREATMENT OF BURN WOUNDS

Yıl 2023, Cilt: 47 Sayı: 3, 1041 - 1052, 20.09.2023

Umay Merve Güven , Tilbe Çevikelli , Sanem Songüloğlu , Serpil Demirci Kayıran

https://doi.org/10.33483/jfpau.1319262

Öz

Objective: In this study, topically applied in situ gel formulations were aimed to design for the modulation of burns, with the active ingredient lidocaine and the gel gained from the Aloe vera plant. The prepared in situ gels were in the liquid form at the room temperature and gelled at the body temperature and adhered to the wound surface, resulting in higher drug residence time. By improving the characteristic properties of the in situ gels, it is aimed to improve patient compliance by obtaining higher local lidocaine concentration.
Material and Method: In situ gel formulations separated by giving different gel codes were examined with characteristic analyses. Within the scope of these examinations, measurement of gelation temperature, pH measurement, in vitro lidocaine release, viscosity and rheological properties and the texture profile of the formulations were determined.
Result and Discussion: Poloxamer 407 based in situ gels designed for topical treatment containing Aloe vera gel and lidocaine have been shown to increase skin residence time. Among the formulations prepared with different content ratios of the polymers Poloxamer 407, Poloxamer 188, HPMC and CMC, the gels coded F5 and A21 showed acceptable gelation temperature for topical use and sustained lidocaine release for 24 hours. According to these findings, it can be revealed that Poloxamer 407-HPMC based in situ gel formulation may be an effective alternative for topical burn treatment.

Anahtar Kelimeler

Aloe vera, burn treatment, in situ gel, lidocaine, topical formulation

YANIK TEDAVİSİNDE KULLANILMAK ÜZERE LİDOKAİN İÇEREN ALOE VERA JEL FORMÜLASYONUNUN HAZIRLANMASI VE İN VİTRO KARAKTERİZASYONU

Öz

Amaç: Bu çalışma kapsamında Aloe vera bitkisinden elde edilen jelin, lidokain etken maddesi ile birlikte yanık tedavisinde topikal olarak uygulanacak in situ jel formülasyonlarının geliştirilmesi amaçlanmıştır. Formülasyonların karakteristik özellikleri iyileştirilerek, oda sıcaklığında sıvı formda olan in situ jellerin vücut sıcaklığında jelleşerek yara yüzeyine yapışma suretiyle daha yüksek lokal ilaç konsantrasyonu elde edilerek hasta uyuncunun artırılması hedeflenmiştir.
Gereç ve Yöntem: Farklı jel kodları verilerek ayrılan in situ jel formülasyonlarının karakteristik özellikleri analiz edilmiştir. Bu incelemeler kapsamında jelleşme sıcaklığının tespiti, pH ölçümü, in vitro lidokain salım çalışması gerçekleştirilmiş ve in situ jellerin viskozite ve reolojik özellikleri ile tekstür profil analizleri değerlendirilmiştir.
Sonuç ve Tartışma: Aloe vera jeli ve lidokain içeren, topikal tedavi için tasarlanmış Poloxamer 407 bazlı in situ jellerin deri üzerinde kalış süresini uzattığı ve lokal lidokain konsantrasyonunu artırabileceği belirlenmiştir. Poloxamer 407, Poloxamer 188, HPMC ve CMC’nin farklı oranları ile hazırlanan in situ jel formülasyonları arasında F5 ve A21 kodlu jeller topikal kullanım için kabul edilebilir jelleşme sıcaklığı göstermiş ve 24 saat lidokain salımı gerçekleştirmiş olup, Aloe vera ve lidokain içeren Poloxamer 407-HPMC bazlı in situ jel formülasyonunun topikal yanık tedavisinde etkili bir alternatif olabileceği sonucuna varılmıştır.

Anahtar Kelimeler

Aloe vera, in situ jel, lidokain, topikal formülasyon, yanık tedavisi

Kaynakça

• 1. Evers, L.H., Bhavsar, D., Mailänder, P. (2010). The biology of burn injury. Experimental Dermatology, 19(9), 777-783. [CrossRef]
• 2. Şakrak, T., Köse, A.A., Karabağlı, Y., Çetin, C. (2011). Yanık ünitemizde yatarak tedavi gören hastalara ait 10 yıllık tarama sonuçlarımız. Türk Plastik Rekonstrüktif ve Estetik Cerrahi Dergisi, 18(3), 111-115.
• 3. Greenhalgh, D.G. (2019). Management of burns. New England Journal of Medicine, 380(24), 2349-2359. [CrossRef]
• 4. Atiyeh, B.S., Gunn, S.W., Hayek, S.N. (2005). State of the art in burn treatment. World Journal of Surgery, 29(2), 131-148. [CrossRef]
• 5. Göç, F., Mat, A., (2019). Türkiye’de yanık tedavisinde geleneksel olarak kullanılan bitkiler. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2(1), 15-35.
• 6. Demirezer, Ö., Saraçoğlu, İ., Şener, B., Köroğlu, A., Yalçın, F.N. (2017). FFD Monografları Bitkiler ve Etkileri. Akademisyen Kitabevi, Ankara.
• 7. Akinyele, B.O., Odiyi, A.C. (2007). Comparative study of vegetative morphology and the existing taxonomic status of Aloe vera L. Journal of Plant Sciences, 2(5), 558-563. [CrossRef]
• 8. Hamman, J.H. (2008). Composition and applications of Aloe vera leaf gel. Molecules, 13(8), 1599-1616. [CrossRef]
• 9. Misir, J., Brishti, F.H., Hoque, M.M. (2014). Aloe vera gel as a novel edible coating for fresh fruits: A review. American Journal of Food Science and Technology, 2(3), 93-97. [CrossRef]
• 10. Vázquez, B., Avila, G., Segura, D., Escalante, B. (1996). Antiinflammatory activity of extracts from Aloe vera gel. Journal of Ethnopharmacology, 55(1), 69-75. [CrossRef]
• 11. Tabandeh, M.R., Oryan, A., Mohammadalipour, A. (2014). Polysaccharides of Aloe vera induce MMP-3 and TIMP-2 gene expression during the skin wound repair of rat. International Journal of Biological Macromolecules, 65, 424-430. [CrossRef]
• 12. Barcroft, A., Myskja, A. (2003). Aloe vera: Nature's Silent Healer. BAAM, London.
• 13. Sari, A.O., Bilgin, O., Bilgiç, A., Nedret, T., Güvensen, A., Şenol, S.G. (2010). Ege ve Güney Marmara bölgelerinde halk ilacı olarak kullanılan bitkiler. Anadolu Ege Tarımsal Araştırma Enstitüsü Dergisi, 20(2), 1-21.
• 14. Rodriguez-Bigas, M., Cruz, N.I., Suarez, A. (1988). Comparative evaluation of Aloe vera in the management of burn wounds in guinea pigs. Plastic and Reconstructive Surgery, 81(3), 386-389. [CrossRef]
• 15. Fozzard, H.A., Sheets, M.F., Hanck, D.A. (2011). The sodium channel as a target for local anesthetic drugs. Frontiers in Pharmacology, 2, 68. [CrossRef]
• 16. Garutti, I., Rancan, L., Simón, C., Cusati, G., Sanchez-Pedrosa, G., Moraga, F., Olmedilla, L., Lopez-Gil, M.T., Vara, E. (2014). Intravenous lidocaine decreases tumor necrosis factor alpha expression both locally and systemically in pigs undergoing lung resection surgery. Anesthesia & Analgesia, 119(4), 815-828. [CrossRef]
• 17. Wen, F., Liu, Y., Wang, H., Tang, W., Hou, Y.D., Wang, H.L. (2017). Lidocaine inhibits the production of IL-1β from macrophages RAW264. 7 induced with lipopolysaccharide. International Journal of Clinical And Experimental Pathology, 10(6), 6582-6588.
• 18. Singh Malik, D., Mital, N., Kaur, G. (2016). Topical drug delivery systems: A patent review. Expert Opinion on Therapeutic Patents, 26(2), 213-228. [CrossRef]
• 19. Torin Huzil, J., Sivaloganathan, S., Kohandel, M., Foldvari, M. (2011). Drug delivery through the skin: Molecular simulations of barrier lipids to design more effective noninvasive dermal and transdermal delivery systems for small molecules, biologics, and cosmetics. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 3(5), 449-462. [CrossRef]
• 20. Elias, P.M. (1988). Structure and function of the stratum corneum permeability barrier. Drug Development Research, 13(2‐3), 97-105. [CrossRef]
• 21. Chang, R.K., Raw, A., Lionberger, R., Yu, L. (2013). Generic development of topical dermatologic products: formulation development, process development, and testing of topical dermatologic products. The AAPS Journal, 15(1), 41-52. [CrossRef]
• 22. Kumar, D., Jain, N., Gulati, N., Nagaich, U. (2013). Nanoparticles laden in situ gelling system for ocular drug targeting. Journal of Advanced Pharmaceutical Technology & Research, 4(1), 9. [CrossRef]
• 23. Madan, M., Bajaj, A., Lewis, S., Udupa, N., Baig, J.A. (2009). In situ forming polymeric drug delivery systems. Indian Journal of Pharmaceutical Sciences, 71(3), 242. [CrossRef]
• 24. Üstündağ Okur, N., Yoltaş, A., Yozgatlı, V. (2016). Development and characterization of voriconazole loaded in situ gel formulations for ophthalmic application. Turkish Journal of Pharmaceutical Sciences, 13(3), 311-317. [CrossRef]
• 25. Liu, L., Gao, Q., Lu, X., Zhou, H. (2016). In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration. Asian Journal of Pharmaceutical Sciences, 11(6), 673-683. [CrossRef]
• 26. Peppas, N.A., Langer, R. (1994). New challenges in biomaterials. Science, 263(5154), 1715-1720. [CrossRef]
• 27. Ali Ibrahim, E.S., Ismail, S., Fetih, G., Shaaban, O., Hassanein, K., Abdellah, N H. (2012). Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharmaceutica, 62(1), 59-70. [CrossRef]
• 28. Okur, M.E., Ayla, Ş., Batur, Ş., Yoltaş, A., Genç, E., Pertek, S., Üstündağ Okur, N. (2019). Evaluation of in situ gel containing pycnogenol for cutaneous wound healing. Medeniyet Medical Journal. 34(1), 67-75. [CrossRef]
• 29. Ur-Rehman, T., Tavelin, S., Gröbner, G. (2011). Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels. International Journal of Pharmaceutics, 409(1-2), 19-29. [CrossRef]
• 30. Koşka, E.T. (2013). Master's Thesis. Administration and experimentation of polyacrylate based hydrogel microspheres for prolonging the activity period of lidocaine (2-diethylamino-n-(2,6 dimethylphenyl) acetamide) as a local anaesthetic. Department of Bioengineering, Faculty of Engineering, Hacettepe University, Ankara, Turkey.
• 31. Guideline IHT. (2005). Validation of analytical procedures: Text and methodology. Q2 (R1), 1(20), 05.
• 32. Chang, J.Y., Oh, Y.K., Choi, H.G., Kim, Y.B., Kim, C.K. (2002). Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. International Journal of Pharmaceutics, 241(1), 155-163. [CrossRef]
• 33. Liu, X., Gan, H., Hu, C., Sun, W., Zhu, X., Meng, Z., Dou, G. (2019). Silver sulfadiazine nanosuspension-loaded thermosensitive hydrogel as a topical antibacterial agent. International Journal of Nanomedicine, 14, 289. [CrossRef]
• 34. Ijaz, N., Durrani, A.I., Rubab, S., Bahadur, S. (2022). Formulation and characterization of Aloe vera gel and tomato powder containing cream. Acta Ecologica Sinica, 42(2), 34-42. [CrossRef]
• 35. Ishihara, M., Nakanishi, K., Ono, K., Sato, M., Kikuchi, M., Saito, Y., Yura, H., Matsui, T., Hattori, H., Uenoyama, M., Kurita, A. (2002). Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials, 23(3), 833-840. [CrossRef]
• 36. Mohamad, N., Amin, M.C.I.M., Pandey, M., Ahmad, N., Rajab, N.F. (2014). Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: Accelerated burn wound healing in an animal model. Carbohydrate Polymers, 114, 312-320. [CrossRef]
• 37. Balakrishnan, B., Mohanty, M., Umashankar, P.R., Jayakrishnan, A. (2005). Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials, 26(32), 6335-6342. [CrossRef]
• 38. Hubbell, J.A. (1996). Hydrogel systems for barriers and local drug delivery in the control of wound healing. Journal of Controlled Release, 39(2-3), 305-313. [CrossRef]
• 39. Rehman, K., Zulfakar, M.H. (2014). Recent advances in gel technologies for topical and transdermal drug delivery. Drug Development and Industrial Pharmacy, 40(4), 433-440. [CrossRef]
• 40. Stanciauskaite, M., Marksa, M., Ivanauskas, L., Perminaite, K., Ramanauskiene, K. (2021). Ophthalmic in situ gels with balsam poplar buds extract: Formulation, rheological characterization, and quality evaluation. Pharmaceutics, 13(7), 953. [CrossRef]
• 41. Joshi, S.C. (2011). Sol-gel behavior of hydroxypropyl methylcellulose (HPMC) in ionic media including drug release. Materials, 4(10), 1861-1905. [CrossRef]
• 42. Wang, M., Xu, L., Hu, H., Zhai, M., Peng, J., Nho, Y., Wei, G. (2007). Radiation synthesis of PVP/CMC hydrogels as wound dressing. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 265(1), 385-389. [CrossRef]
• 43. Iwu, M.M. (1993). Handbook of African medicinal plants. CRC Press, Maryland, p.183-184.
• 44. Aksu, N.B., Yozgatlı, V., Okur, M.E., Ayla, Ş., Yoltaş, A., Okur, N.Ü. (2019). Preparation and evaluation of QbD based fusidic acid loaded in situ gel formulations for burn wound treatment. Journal of Drug Delivery Science and Technology, 52, 110-121. [CrossRef]
• 45. Joshi, N., Mishra, N., Rai, V.K. (2021). Development and evaluation of in situ gel of silver sulfadiazine for improved therapeutic efficacy against infectious burn wound. Journal of Pharmaceutical Innovation, 16(3), 537-550. [CrossRef]
• 46. Majeed, A., Khan, N.A. (2019). Ocular in situ gel: An overview. Journal of Drug Delivery and Therapeutics, 9(1), 337-347. [CrossRef]
• 47. Proksch, E. (2018). pH in nature, humans and skin. The Journal of Dermatology, 45(9), 1044-1052. [CrossRef]
• 48. Aydin E. (2013). Master's Thesis. Development of a ocular nanosystem formulation containing a nonsteroidal anti-inflammatory drug. Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
• 49. Okur, N.Ü., Yozgatli, V., Şenyiğit, Z. (2020). Formulation and detailed characterization of voriconazole loaded in situ gels for ocular application. Journal of Faculty of Pharmacy of Ankara University, 44(1), 33-49. [CrossRef]
• 50. Owczarz, P., Rył, A., Wichłacz, Ż. (2019). Application of texture profile analysis to investigate the mechanical properties of thermosensitive injectable chitosan hydrogels. Progress on Chemistry and Application of Chitin and its Derivatives, 24, 151-163. [CrossRef]
• 51. Patlolla, V.G.R., Peter Holbrook, W., Gizurarson, S., Kristmundsdottir, T. (2019). Doxycycline and monocaprin in situ hydrogel: Effect on stability, mucoadhesion and texture analysis and in vitro release. Gels, 5(4), 47. [CrossRef]
• 52. Koffi, A.A., Agnely, F., Ponchel, G., Grossiord, J.L. (2006). Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine. European Journal of Pharmaceutical Sciences, 27(4), 328-335. [CrossRef]